tbuckley/cabot-search huggingface dataset:
COVID-19 in the 47 countries of the WHO African region: a modelling analysis of past trends and future patterns
Authors: Joseph Waogodo Cabore, Humphrey Cyprian Karamagi, Hillary Kipchumba Kipruto, Joseph Kyalo Mungatu, James Avoka Asamani, Benson Droti, Regina Titi-ofei, Aminata Binetou Wahebine Seydi, Solyana Ngusbrhan Kidane, Thierno Balde, Abdou Salam Gueye, Lindiwe Makubalo, Matshidiso R Moeti
Journal: The Lancet Global Health (2022)

BackgroundCOVID-19 has affected the African region in many ways. We aimed to generate robust information on the transmission dynamics of COVID-19 in this region since the beginning of the pandemic and throughout 2022.MethodsFor each of the 47 countries of the WHO African region, we consolidated COVID-19 data from reported infections and deaths (from WHO statistics); published literature on socioecological, biophysical, and public health interventions; and immunity status and variants of concern, to build a dynamic and comprehensive picture of COVID-19 burden. The model is consolidated through a partially observed Markov decision process, with a Fourier series to produce observed patterns over time based on the SEIRD (denoting susceptible, exposed, infected, recovered, and dead) modelling framework. The model was set up to run weekly, by country, from the date the first infection was reported in each country until Dec 31, 2021. New variants were introduced into the model based on sequenced data reported by countries. The models were then extrapolated until the end of 2022 and included three scenarios based on possible new variants with varying transmissibility, severity, or immunogenicity.FindingsBetween Jan 1, 2020, and Dec 31, 2021, our model estimates the number of SARS-CoV-2 infections in the African region to be 505·6 million (95% CI 476·0–536·2), inferring that only 1·4% (one in 71) of SARS-CoV-2 infections in the region were reported. Deaths are estimated at 439 500 (95% CI 344 374–574 785), with 35·3% (one in three) of these reported as COVID-19-related deaths. Although the number of infections were similar between 2020 and 2021, 81% of the deaths were in 2021. 52·3% (95% CI 43·5–95·2) of the region's population is estimated to have some SARS-CoV-2 immunity, given vaccination coverage of 14·7% as of Dec 31, 2021. By the end of 2022, we estimate that infections will remain high, at around 166·2 million (95% CI 157·5–174·9) infections, but deaths will substantially reduce to 22 563 (14 970–38 831).InterpretationThe African region is estimated to have had a similar number of COVID-19 infections to that of the rest of the world, but with fewer deaths. Our model suggests that the current approach to SARS-CoV-2 testing is missing most infections. These results are consistent with findings from representative seroprevalence studies. There is, therefore, a need for surveillance of hospitalisations, comorbidities, and the emergence of new variants of concern, and scale-up of representative seroprevalence studies, as core response strategies.FundingNone.
Molecular mechanism in urothelial carcinoma with FGFR3 mutation.
Authors: Huanhuan Liu, Yanrui Zhang, Feng Lou, Shanbo Cao, Huina Wang
Journal: Journal of Clinical Oncology (2022)

e16548 Background: Specific genomic alterations in the FGFR (fibroblast growth factor receptor) family are well-known to be characteristic driver events of urothelial carcinoma and is a therapeutic target. However, molecular mechanism differences of urothelial carcinoma (UC) stratified by the FGFR mutation status has not yet been described. Methods: Patients diagnosed with UC were enrolled in the study. Tumor tissue and matching blood were sequenced by next-generation sequencing (NGS) techniques with Acornmed panel with 808 cancer-related genes. Results: A total of 368 patients with UC were enrolled including 75 patients with FGFR2/3 mutation and 293 patients with FGFR2/3 wildtype. In FGFR2/3 mutation cohorts, the five most frequently mutated genes were FGFR2/3 (100%), KMT2D (56%), KMT2C (35%), CREBBP (32%) and FAT1 (31%). For FGFR2/3 wildtype cohorts, the five most frequently mutated genes were TP53 (46%), KMT2D (41%), BRD4 (23%), ARID1A (15%), and KMT2C (14%). 87 frequently mutated genes were significant difference between FGFR2/3 mutation and FGFR2/3 wildtype cohorts, such as KMT2D, KMT2C, STAG2, CREBBP and FAT1, excluding the FGFR2/3 gene. Signature 1 for spontaneous deamination of 5−methylcytosine and signature 22 for exposure to aristolochic acid (AA) existed in both cohorts. Although there were APOBEC Cytidine Deaminase signatures in both groups, they were projected to different COSMIC signatures (signature 2 and 13, respectively). Signature 10 for defects in polymerase POLE (4.81%) were only observed in the FGFR2/3 mutation cohorts. In the FGFR2/3 mutation cohorts, mutated genes were mainly enriched in the cancer pathway, PI3K-Akt signaling pathway, and Ras signaling pathway. However, in the FGFR2/3 wildtype cohorts, the primary pathways included the cancer pathway, PI3K-Akt signaling pathway, and Rap1 signaling pathway. Conclusions: There were characterized the genomic differences and similarities, stratified by the TP53 status, which may reflect the UC patients with TP53 mutation harbored specific molecular mechanism.
DIPG-64. Feasibility and early results of radiotherapy, concomitant nimotuzumab and vinorelbine and re-irradiation at progression, for newly diagnosed childhood and adolescence diffuse midline glioma (DMG)
Authors: Elisabetta Schiavello, Veronica Biassoni, Francesco Barretta, Giovanna Gattuso, Emilia Pecori, Lorenza Gandola, Luna Boschetti, Angela Mastronuzzi, Antonella Cacchione, Lucia Quaglietta, Claudia Milanaccio, Fabio Simonetti, Francesca Romana Buttarelli, Manila Antonelli, Maura Massimino
Journal: Neuro-Oncology (2022)

Abstract BACKGROUND: The purposes of this trial were evaluating the feasibility, response and PFS/OS of patients receiving upfront radiotherapy and reirradiation at progression with concomitant nimotuzumab/vinorelbine chemotherapy as the standard arm of the ongoing protocol for DIPG. METHODS: Patients aged 2-21 years with not-pretreated DMG (evidence of H3.3K27M mutation at immunohistochemistry) received vinorelbine 20 mg/m2+nimotuzumab 150 mg/m2 weekly for 12 weeks; thereafter every other week until tumor progression or for up to 2 years. Focal photons irradiation was delivered within the 3rd week after first nimotuzumab+vinorelbine administration with a total dose of 54 Gy in 1.8 Gy daily fractions. For local progression re-irradiation was proposed at 19.8 Gy; in case of dissemination craniospinal-irradiation at 36 Gy was adopted. MRI were blindly centrally reviewed at diagnosis and every 12 weeks thereafter. RESULTS: Aggregated preliminary results are available for 20 patients from 4 Italian centers: 12 males, median age 11 years (range 3-17). Median time of observation was 12.5 months; 8 had thalamic/basal ganglia disease, in 5 pons was involved (2 pontobulbar, 3 pontomesencephalic), 6 spinal, 2 cerebellar. 13 patients had only biopsy, the others partial or near-total resection.14 relapsed: 5 locally, 4 with dissemination, 5 with both; 12 died, one was lost at follow-up. Two patients received reirradiation, one of them was irradiated three times without evidence of radionecrosis, still alive at 26 months from diagnosis. Median EFS/OS were 8.3/10.2 months, respectively; EFS/OS at 1 year were 25.8/36.7%. Survival curves between spinal and cerebral locations showed no difference. Patients after partial/near-total resection vs biopsied seemed to have earlier relapses (P 0.017) with EFS at 6 months of 34.3/75.0% respectively. CONCLUSIONS: This is one of the first series of DMG homogeneously and prospectively treated; treatment was feasible. A potential role of reirradiation emerge as in DIPGs.
Melatonin effect on sleep disorders in breast cancer patients receiving adjuvant chemotherapy.
Authors: Abdolali Shahrasbi, Nasrin Einei, Mohsen Esfandbod, Kamran Derakhshan
Journal: Journal of Clinical Oncology (2022)

e12512 Background: Sleep disturbances in breast cancer patients who have received chemotherapy are among the most common causes of decreased quality of life during breast cancer treatment. Melatonin is an endogenous hormone and its secretion level is directly related to sleep quality. Melatonin supplements may help with certain conditions, such as delayed sleep-wake phase disorder. In this study, we investigated the effect of melatonin pills in treating sleep disorders in patients diagnosed with invasive breast cancer and who were received adjuvant chemotherapy. Methods: In this randomized clinical trial (before and after), 25 breast cancer patients aged 40 to 60 years who were under adjuvant chemotherapy drugs and had sleep disorders Pittsburg sleep quality index (PSQI) &lt; 5, were enrolled. All the patients were interviewed by a psychiatrist and learned about the Pittsburg questionnaire and filled it out personally. They were evaluated in three phases before starting chemotherapy, one month and three months later. Melatonin was administered orally at a dose of 6mg per night. Then, the effects of melatonin on sleep disorders were determined by the questionnaire and compared by analysis of variance (ANOVA tool) and required statistical analysis. Results: In our study, all cases were women with a mean age of 48.4 ± 6.3 years. In general, all the different domains of sleep components except the “sleeping pills” section were significantly improved during the study period. Over the first 30-days, total score, sleep quality, sleep duration, sleep delay, and daily performance improved considerably. By the end of day 90, sleep efficiency and sleep disorders also became better (table). Conclusions: Melatonin well affects the sleep condition of breast cancer patients who received adjuvant chemotherapy, and this effect persists with the continuation of the treatment plan.[Table: see text]
Outcomes of Salvage Robot-Assisted Radical Prostatectomy (S-RARP) post focal ablation for prostate cancer in comparison with primary Robot-assisted Radical Prostatectomy (RARP); a matched analysis
Authors: S. Bhat, M. Covas Moschovas, J. Noel, T. Rogers, R. Pereira, S. Reddy, M. Sandri, V. Patel
Journal: European Urology (2022)
Updated overall survival (OS) data from the phase 1b study of tebentafusp (tebe) as monotherapy or combination therapy with durvalumab (durva) and/or tremelimumab (treme) in metastatic cutaneous melanoma (mCM).
Authors: Mark R. Middleton, Omid Hamid, Alexander Noor Shoushtari, Friedegund Elke Meier, Todd Michael Bauer, April K.S. Salama, John M. Kirkwood, Paolo Antonio Ascierto, Paul Lorigan, Cornelia Mauch, Marlana M. Orloff, T.R. Jeffry Evans, Shaad Essa Abdullah, Yuan Yuan, James Mitchell, Jessica Cecile Hassel
Journal: Journal of Clinical Oncology (2022)

104 Background: Tebe is a T-cell receptor bispecific (gp100 x CD3) against gp100 peptide-HLA-A2 complexes that are overexpressed in uveal (UM)/cutaneous melanoma (CM). Tebe is the only therapy to show an OS benefit (HR 0.51) in a phase (Ph) 3 trial in previously untreated metastatic UM. In a prior Ph 1 trial, tebe demonstrated monotherapy activity in anti-PD1 naïve mCM (1-yr OS, approx. 74%). The safety and initial activity of tebe with dose escalation of durva and/or treme in previously treated mCM has been reported. Here, we present updated OS in the subset of mCM patients (pts) relapsed or refractory to prior anti-PD1, a population where recent reports suggest a benchmark 1-yr OS of approximately 55% and median OS of approximately 14 months (mos). Methods: Patients with HLA-A2+, pre-treated mCM received weekly tebe (IV) monotherapy in Arm 4a or in combination with dose escalation of durva and/or treme (IV) on day 15 of each cycle (Arms 1-3). Primary objective was RP2D, secondary objectives were safety and efficacy. Subgroup analyses were performed for durva doses ≥10 mg/kg, a threshold previously defined by Bavarel et al, 2018. Analysis performed on data cut-off 04 January 2022 with median follow up for 14.3 mos. [NCT02535078] Results: 112 pts were treated with median age 59, 23% were ECOG = 1, 37% were BRAFm (73% received prior BRAFi/MEKi), 55% had LDH &gt; ULN. 92% of pts were 2L+ and 74% 3L+; median 3 prior lines. The safety profile of all therapy arms within this study therapy remains very favorable with no new safety signals identified. 97 of 112 pts were documented as relapsed or refractory to prior anti-PD1 (80% also received ipilimumab). Of these 97 pts, 32 received tebe + durva (Arm 1), 13 received tebe + treme (Arm 2), 26 received triplet therapy (Arm 3), and 20 received tebe monotherapy (Arm 4a). 33 of 97 pts in any arm received durva ≥ 10 mg/kg with 1-yr OS of 79%, 2-yr OS of 34%, and median OS of 20 mos. 64 of 97 pts received durva &lt; 10 mg/kg with 1-yr OS of 53%, 2-yr OS of 24%, and median OS of 13 mos. Tebe + durva doublet therapy had similar OS to triplet therapy with tebe + durva + treme: 1-yr OS of 74% vs. 76%, and 2-yr OS of 32% vs. 27%, respectively. Conclusions: Promising OS is seen in mCM similar to mUM, with both tumor types overexpressing gp100. In mCM relapsed or refractory to prior anti-PD1, tebe with anti–PD-L1 continues to demonstrate promising OS (1-yr, approx. 75%) compared to recent benchmarks (1-yr, approx. 55%). These data provide rationale for a randomized study of tebe with anti-PD(L)1 in mCM. Clinical trial information: NCT02535078.
A Prehospital Triage System to Detect Traumatic Intracranial Hemorrhage Using Machine Learning Algorithms
Authors: Daisu Abe, Motoki Inaji, Takeshi Hase, Shota Takahashi, Ryosuke Sakai, Fuga Ayabe, Yoji Tanaka, Yasuhiro Otomo, Taketoshi Maehara
Journal: JAMA Network Open (2022)

<h3>Importance</h3> An adequate system for triaging patients with head trauma in prehospital settings and choosing optimal medical institutions is essential for improving the prognosis of these patients. To our knowledge, there has been no established way to stratify these patients based on their head trauma severity that can be used by ambulance crews at an injury site. <h3>Objectives</h3> To develop a prehospital triage system to stratify patients with head trauma according to trauma severity by using several machine learning techniques and to evaluate the predictive accuracy of these techniques. <h3>Design, Setting, and Participants</h3> This single-center retrospective cohort study was conducted by reviewing the electronic medical records of consecutive patients who were transported to Tokyo Medical and Dental University Hospital in Japan from April 1, 2018, to March 31, 2021. Patients younger than 16 years with cardiopulmonary arrest on arrival or with a significant amount of missing data were excluded. <h3>Main Outcomes and Measures</h3> Machine learning–based prediction models to detect the presence of traumatic intracranial hemorrhage were constructed. The predictive accuracy of the models was evaluated with the area under the receiver operating curve (ROC-AUC), area under the precision recall curve (PR-AUC), sensitivity, specificity, and other representative statistics. <h3>Results</h3> A total of 2123 patients (1527 male patients [71.9%]; mean [SD] age, 57.6 [19.8] years) with head trauma were enrolled in this study. Traumatic intracranial hemorrhage was detected in 258 patients (12.2%). Among several machine learning algorithms, extreme gradient boosting (XGBoost) achieved the mean (SD) highest ROC-AUC (0.78 [0.02]) and PR-AUC (0.46 [0.01]) in cross-validation studies. In the testing set, the ROC-AUC was 0.80, the sensitivity was 74.0% (95% CI, 59.7%-85.4%), and the specificity was 74.9% (95% CI, 70.2%-79.3%). The prediction model using the National Institute for Health and Care Excellence (NICE) guidelines, which was calculated after consultation with physicians, had a sensitivity of 72.0% (95% CI, 57.5%-83.8%) and a specificity of 73.3% (95% CI, 68.7%-77.7%). The McNemar test revealed no statistically significant differences between the XGBoost algorithm and the NICE guidelines for sensitivity or specificity (<i>P</i> = .80 and<i>P</i> = .55, respectively). <h3>Conclusions and Relevance</h3> In this cohort study, the prediction model achieved a comparatively accurate performance in detecting traumatic intracranial hemorrhage using only the simple pretransportation information from the patient. Further validation with a prospective multicenter data set is needed.
HGG-57. Barriers in the management of pediatric high-grade gliomas in a low-resource setting during the COVID era
Authors: Kirby Manigos, Oliver Ryan Malilay, Joseph Erroll Navarro, Kenny Seng, Jose Carlos Alcazaren, Jared Paul Golditum, Ronnie Baticulon
Journal: Neuro-Oncology (2022)

Abstract INTRODUCTION: High-grade gliomas account for &amp;lt;5% of all pediatric brain tumors with a 20% 5-year overall survival even with maximal safe resection followed by concurrent radiotherapy and chemotherapy. Patients in low- and middle-income countries already face delays and barriers to the treatment they require. The current COVID pandemic has added unique challenges to the delivery of complex, multidisciplinary health services to these patients. METHODOLOGY AND RESULTS: We retrospectively reviewed the records of four patients, ages 2-18 years old, with histologically confirmed high-grade glioma managed in a tertiary government institution from 2020-2021. Three of the patients had a supratentorial tumor and one patient had multiple tumors located in both supra- and infratentorial compartments. Neurosurgical procedures performed were: gross total excision (1), subtotal excision (2), and biopsy (1). The tissue diagnoses obtained were glioblastoma (3) and high-grade astrocytoma (1). Two patients survived and are currently undergoing adjuvant radiotherapy and chemotherapy. The remaining two patients expired: one from hospital-acquired pneumonia and the other from COVID-19 infection. DISCUSSION: Decreased mobility due to lockdowns, the burden of requiring negative COVID-19 results before admission for surgery, reduced hospital capacity to comply with physical distancing measures, the postponement of elective surgery to minimize COVID-19 transmission, physician and nursing shortages due to infection or mandatory isolation of staff, cancellation of face-to-face outpatient clinics, and hesitation among patients and their families to go to the hospital for fear of exposure were found to be common causes of delays in treatment. Also, the redirection of health resources and other government and hospital policies to handle the COVID-19 pandemic resulted in an overall delay in the delivery of health services. In particular, the management of pediatric patients with cancers, especially high-grade gliomas, was significantly disrupted.
Re: Katharina Beyer, Lisa Moris, Michael Lardas, et al. Updating and Integrating Core Outcome Sets for Localised, Locally Advanced, Metastatic, and Nonmetastatic Castration-resistant Prostate Cancer: An Update from the PIONEER Consortium. Eur Urol 2022;81:503–14
Authors: Ruobing Lei, Yuehuan Li, Yaolong Chen
Journal: European Urology (2022)
Oncologist knowledge of cost of genetic testing.
Authors: Shayna Weiner, Sarah Austin, Grant Carr, Kelley M. Kidwell, Ken Resnicow, Elena Martinez Stoffel, Jennifer J. Griggs
Journal: Journal of Clinical Oncology (2022)

10591 Background: Genetic testing allows patients and their families to identify hereditary cancer syndromes. Financial barriers to genetic testing are a major concern for patients offered genetic risk assessment. The cost of germline genetic testing has decreased substantially over the last several years. It is not clear, however, that oncologists are knowledgeable about the cost of genetic testing. The purpose of this study was to investigate oncologists’ knowledge of genetic testing costs. Methods: We deployed a survey to all oncologists who are members of the Michigan Oncology Quality Consortium, a physician-led quality improvement collaborative whose members represent 95% of the oncologists in Michigan. The modified Dillman method was used to achieve the maximum response rate. Responses were collected from December 2020 through May 2021. The responses to the question, “If a patient were to ask you how much it would cost for them to have clinical genetic testing for hereditary cancer syndromes, what would you tell them?” were independently coded by three investigators into one of three categories – correct and helpful, correct and not helpful, or incorrect and not helpful. We investigated associations between the number of years in practice and how important was cost as a barrier to genetic risk assessment. Results: The response rate to the survey was 61.2% (194/317). Only 25% of respondents provided an answer that was deemed to be both correct and helpful to a patient, for example “approximately $250 if out of pocket.” Nearly 40% of respondents gave an answer that was correct but was non-specific and would not help a patient decide about pursuing genetic testing. This category included responses such as deferring to a genetic counselor or that cost varies based on insurance. About 28% gave an incorrect response, such as “several thousand dollars” or responded, “I don’t know.” No associations were found between cost response category, number of years in practice, or reported responses that financial barriers play a role in referral patterns. Conclusions: The majority of oncologists in our statewide sample do not have an accurate understanding of the cost of germline genetic testing. Lack of precise information about the costs of testing may lead patients to believe that genetic testing is either not important or not within reach. Furthermore, providing incorrect information can have a downstream effect and prevent patients and their families from pursuing genetic counseling. Improving oncologists’ knowledge about the cost of testing may decrease barriers to uptake of genetic risk assessment. [Table: see text]